A number of diseases or disorders are caused by inadequate levels of a certain polypeptide in the body or by the production of defective versions of this polypeptide. With the advent of genetic-engineering and molecular biology it is now possible to treat such diseases and disorders by replacement polypeptide therapy. For example, administration of a recombinantly-produced polypeptide can treat a disease or disorder by supplementing the low levels of the endogenous polypeptide or substituting for a defective one being produced by the body.
One factor critical to the design an effective recombinant polypeptide therapy is to increase the circulatory half-life of the polypeptide once administered to the body. The length of time a polypeptide remains active in the body can be extended, e.g., by modifying the polypeptides using a wide variety of functional groups that that increase the half-life of the polypeptide. Such modifications protect the polypeptide against proteolytic degradation, increase its stability, enhance or facilitate its interaction with another molecule, reduce its antigenicity, and/or decrease its clearance rate from the body. Exemplary modifications useful for extending the circulatory half-life of an administered recombinant polypeptide include, without limitation PEGylation, polysialylation, HESylation, Sylation, and citrullination.
An important aspect of developing recombinant polypeptide therapy for diseases or disorders is the ability to measure the polypeptide's activity following a modification and/or administration into an individual. This ability is often hampered, however, by the presence of the endogenous polypeptide that interfere with the specificity and accuracy of assays used to detect the presence or activity of the recombinant polypeptide. Thus, there is a need to develop methods for assessing the presence and/or activity of a recombinant polypeptide.